Managing inflammation in neurocritical care is often desirable. There are a number of indications that could benefit from cooling, including spinal cord injury, traumatic brain injury, head trauma, cerebral ischemia, seizures, fever, thoraco-abdominal aortic aneurysms (TAAA), hydrocephalus, cerebrospinal fluid (CSF) leaks, aneurysmal subarachnoid hemorrhage, and others.
Fever occurs in 20-50% of critically ill neurologic patients and may adversely affect neurologic outcome. Specifically, fever occurs in up to 40% of patients with ischemic stroke and intracerebral hemorrhage and in 40-70% of patients with severe traumatic brain injury or aneurysmal subarachnoid hemorrhage. Fever is independently associated with increased morbidity and mortality after ischemic and hemorrhagic stroke. In subarachnoid hemorrhage and traumatic brain injury patients, temperature elevation has been linked with increased intracranial pressure.
Regarding spinal cord injury, although significant damage is caused by the mechanics of the traumatic spinal cord injury, secondary injury that follows is often even more dangerous. It occurs within the first 12-24 hours following the injury and can last up to 5-10 days, depending on the severity of the injury. Secondary injury causes physiological disturbances that disrupt the body's homeostasis, such as initiating a cellular inflammatory response at the injury site and increasing the release of free radicals. An overabundance of free radicals contributes to tissue ischemia, cerebral edema, and disruption of the spine-blood barrier. The use of hypothermia as a therapeutic agent has been shown effective in providing neuroprotection from secondary injury. Research has shown the benefits of hypothermia include decreasing oxygen consumption, free radical generation, neurotransmitter release, inflammation, and metabolic demands. Even a temperature decrease of 1-2° C. can be beneficial at the cellular level.
As disease awareness and diagnostic modalities continue to improve, the prevalence of thoracic and thoracoabdominal aortic aneurysm (TAAA and dissection) is increasing, affecting up to 16.3 individuals per 100,000 per year. Paraplegia remains one of the most devastating complications of thoracoabdominal aortic surgery, and is associated with a significant increase in both morbidity and mortality. Both pharmacological and mechanical modalities used to control central hypertension during aortic occlusion affect CSF dynamics and spinal cord perfusion pressure. Although lumbar drainage has been successfully used for TAAA patients for over 10 years, their introduction to TAAA as standard of care has been slow to evolve. In fact, lumbar drainage has cut the rate of paraplegia from 30% to 10-15% and the growth of minimally invasive TEVAR procedures has meant that the rate is now conservatively estimated at about 5-7%. This still means that approximately 15,500 people die or experience permanent weakness and disability each year. The two main approaches to protect the spinal cord during TAAA repair include maximizing spinal cord perfusion and inducting systemic hypothermia. Regional hypothermia may have fewer side effects, but epidural cooling can cause a sharp increase in CSF pressure and attenuate spinal cord perfusion.
Traumatic brain injury is a major source of death and severe disability worldwide. In the United States alone, 1.7 million people suffer a traumatic brain injury each year. Approximately 52,000 people die and 80,000 remain permanently disabled. Therapeutic hypothermia can be an effective intervention to reduce intracranial pressure and protect against secondary ischemic neuronal injury. Despite its therapeutic benefit, systemic hypothermia is associated with many potential side effects that have limited its widespread use including depth of cooling, coagulopathies, shivering, arrhythmias, and immune suppression, with increased susceptibility to infection and electrolyte imbalance. Furthermore, following a traumatic brain injury, a variety of inflammatory cytokines (e.g. IL-1, IL-6, and TNF) have been shown to worsen neuroinflammation, contribute to secondary brain damage and worse long-term outcomes.
Current methods for cooling include inducing systemic hypothermia in a patient, the use of cooling helmets, cooling the patient's blood, and circulating coolant through a closed loop within the CSF space. Typical ranges of systemic hypothermia include 32° C. to 34° C. There are several reasons why hypothermia is challenging to implement clinically despite its benefits. Current hypothermia methods can cause serious adverse events, such as arrhythmias, infection, sepsis, coagulopathy, electrolyte abnormalities, mild acidosis, a rise in lactate levels/amylase levels, excessive localized cooling or necrosis, skin issues, and other issues. Accordingly, there is a need in the art to provide cooling without the risks of current methods.